A Broad Spectrum of Prolactin Suppression by Bromocriptine in Hyperprolactinemic Women: A Study of Serum Prolactin and Bromocriptine Levels after Acute and Chronic Administration ofBromocriptine*

Abstract

Medical therapy with the semisynthetic ergot, bromocriptine (2-bromo-a-ergocryptine; CB 154), was assessed in 18 hyperprolactinemic women. Serum PRL and bromocriptine levels were measured after a single 2.5-mg oral dose and on chronic treatment at 3 and 6 months. All patients showed a marked decrease in circulating PRL concentrations after the single 2.5-mg dose of bromocriptine. Five patients did not decrease their PRL levels into the normal range on chronic therapy with 7.5 mg/day bromocriptine, although 3 of the 5 returned to normal ovulatory cycles. There is a broad spectrum of responsiveness to bromocriptine among hyperprolactinemic women, with a few patients showing relatively poor suppression; this relative lack of suppressibility persists even after long term treatment and is not correlated with serum levels of bromocriptine.The effective concentration of bromocriptine measured in these patients was approximately 1 x 10~9 M (0.7 ng/ml), very nearly that required for maximal PRL suppression in vitro. The suppression of PRL continued for at least 11 h, with the peak bromocriptine concentration at 3 h, an effect consistent with the in vitro demonstration of prolonged bromocriptine effectiveness.Despite the variability of responsiveness to bromocriptine among hyperprolactinemic women, including a minority who respond less well to bromocriptine in terms of their circulating PRL concentrations, these patients, nevertheless, regain ovulatory menstrual cycles. We believe that these studies present evidence for the presence of a spectrum of dysfunction of dopamine mechanisms at the lactotroph in hyperprolactinemic states. (J Clin Endocrinol Metab 50: 1026 B ROMOCRIPTINE (2-bromo-a-ergocryptine; CB 154), a semisynthetic ergot alkaloid developed for its serum PRL-lowering properties (1), was introduced for clinical testing in 1971. This pharmacological agent now has an established role in the treatment of hyperprolactinemia, both to suppress lactation during the puerperium (2, 3) and in clinical settings not associated with pregnancy, such as PRL-secreting pituitary tumors (4-7). Bromocriptine therapy is capable of stopping or greatly diminishing galactorrhea and reversing the hypogonadism frequently associated with hyperprolactinemia (4-7). Regardless of pretreatment serum PRL levels in patients with or without well documented pituitary

Medical Treatment of Hyperprolactinemia

“…In our studies only 18% of the patients (n = 15) needed a dose of more than 5 mg. 7 among them did not return to normal values with 10 mg and were not given a higher dose, 4 were corrected with 10-15 mg, 1 individual with 20 mg, 2 with 25 mg, and I with 30 mg. The resistance mechanism is unknown, but it does not seem to be related to individual variations in pharmaco kinetics [44], Might it be that certain lactotropic cells of the adenoma have lost their receptivity to dopamine or its agonists? Is there a problem in transport to the receptors?…”

Sensitive and Specific Bromocriptine Radioimmunoassay with Iodine Label: Measurement of Bromocriptine in Human Plasma

“…II The plasma bromocriptine concentration profiles obtained in this study after 2·5 mg bromocriptine orally are broadly similar to those obtained by Thorner et al., using a comparable protocol and a tritium assay employing a similar tripeptide specific antiserum. 12 The product of DHE iodination was not identified but the binding results would suggest that the iodine had been incorporated into the ergoline portion of the molecule as predicted theoretically. An apparently identical product was formed from DHE, as judged by thin layer radiochromatography, using Iodogen'P or Nbromosuccinimide iodination techniques.…”

“…Inter-patient variation in nonspecific binding was small (range 4·5-6·0%) relative to total binding, so it was unnecessary to use a patient's pre-treatment plasma to construct the standard curve for that patient's samples, as has proved necessary in most of the tritium based assays. 12 The standard curves were highly reproducible and between-batch coefficients of variation for bromocriptine controls were less than 10% (Table 1). Within-batch coefficients of variation were 2·3-3·4% at bromocriptine concentrations of 0·5-1·0 nmol/L.…”

“…Tritium methods, although frequently developed using a normal plasma pool to construct standard curves, IlJ in practice, when used to measure patient samples, have to use pretreatment plasma from a patient to make a standard curve for the measurement of that patient's samples. 12 A major advantage of this assay was that, provided plasma samples had been stored frozen for less than 2 months, interpatient variation in non-specific binding was so low relative to antibody bound-counts that several patients' samples could be measured against the same standard curve made in normal pooled plasma.…”

A Giant Prolactinoma and the Effect of Chronic Bromocriptine Therapy on Basal and TRH-Stimulated Serum Prolactin Levels

“…Bromocriptine has been shown to inhibit secretion [5,6], storage in secretory granules [7] and synthesis of pro lactin by blocking the DNA to mRNA transcription of the prolactin gene [8]. The decrease in protein synthesis leads to a reduction in cell size and, in turn, is thought to lead to a proportional reduction in tumor size [9,10].…”